Entering the 21st century: the challenges for development

By many people, the 20th century will be remembered as an era of great achievement in human endeavour, and of enormous economic growth and prosperity. Achievements in medical research, from eradicating infectious diseases to laser surgery; in engineering, from the transistor to space exploration; and in economic development have all contributed to greater well being in the world at the end of the 20th century. Among the challenges to development identified by the World Bank in the coming decades will be managing the twin processes of globalization and localization, as well as post-conflict reconstruction. These will form the backdrop of the Bank''s main focus of creating a world free of poverty.     

Molecules to minds: grand challenges for the 21st century

The Institute of Medicine's Forum on Neuroscience and Nervous System Disorders established a "Grand Challenges Initiative." The goal is to help frame a broad, integrated research program that would attract substantial funding and generate additional resources to support large-scale efforts to tackle some of the most daunting but important neuroscience questions.     

Parasitic diseases: opportunities and challenges in the 21st century

The opportunities and challenges for the study and control of parasitic diseases in the 21st century are both exciting and daunting. Based on the contributions from this field over the last part of the 20th century, we should expect new biologic concepts will continue to come from this discipline to enrich the general area of biomedical research. The general nature of such a broad category of infections is difficult to distill, but they often depend on well-orchestrated, complex life cycles and they often involve chronic, relatively well-balanced host/parasite relationships. Such characteristics force biological systems to their limits, and this may be why studies of these diseases have made fundamental contributions to molecular biology, cell biology and immunology. However, if these findings are to continue apace, parasitologists must capitalize on the new findings being generated though genomics, bioinformatics, proteomics, and genetic manipulations of both host and parasite. Furthermore, they must do so based on sound biological insights and the use of hypothesis-driven studies of these complex systems. A major challenge over the next century will be to capitalize on these new findings and translate them into successful, sustainable strategies for control, elimination and eradication of the parasitic diseases that pose major public health threats to the physical and cognitive development and health of so many people worldwide.     

Green revolution: preparing for the 21st century.

In the 1960s there were large-scale concerns about the world's ability to feed itself. However, widespread adoption of "green revolution" technology led to major increases in food-grain production. Between 1966 and 1990, the population of the densely populated low-income countries grew by 80%, but food production more than doubled. The technological advance that led to the dramatic achievements in world food production over the last 30 years was the development of high-yielding varieties of wheat and rice. These varieties are responsive to fertilizer inputs, are lodging resistant, and their yield potential is 2-3 times that of varieties available prior to the green revolution. In addition, these varieties have multiple resistance to diseases and insects and thus have yield stability. The development of irrigation facilities, the availability of inorganic fertilizers, and benign government policies have all facilitated the adoption of green-revolution technology. In the 1990s, the rate of growth in food-grain production has been lower than the rate of growth in population. If this trend is not reversed, serious food shortages will occur in the next century. To meet the challenge of feeding 8 billion people by 2020, we have to prepare now and develop the technology for raising farm productivity. We have to develop cereal cultivars with higher yield potential and greater yield stability. We must also develop strategies for integrated nutrient management, integrated pest management, and efficient utilization of water and soil resources.     

Tropical medicine for the 21st century.

The specialty of tropical medicine originated from the needs of the colonial era and is removed from many of the health care requirements of tropical countries today. Tropical medicine concentrates on parasitic diseases of warm climates, although other infections and diseases related to poverty rather than climate dominate medicine in developing countries challenged by population pressure, civil strife, and migration. In the new century, tropical medicine would best be absorbed into the specialty of infectious diseases, which should incorporate parasitic diseases, travel medicine, and sexually transmitted diseases. Pressing questions for health care and research in developing countries concern the provision of appropriate services for problems such as HIV/AIDS, tuberculosis, sexually transmitted diseases, and injuries. The question of how to provide appropriate clinical care in resource poor settings for the major causes of morbidity and premature mortality has been neglected by donors, academic institutions, and traditional tropical medicine.     

Oxysterols: novel biologic roles for the 21st century

A major focus for the 21st century are the sterol intermediates in cholesterol synthesis and their metabolites. No longer considered inactive way stations in their transformation to cholesterol, both physiologic and pathophysiologic studies, though early in their development, indicate novel biologic roles for these sterols, and their oxysterol metabolites that bypass cholesterol, the expected end product. A major impetus for further inquiry is the recognition that in genetically determined errors in cholesterol synthesis such as Smith-Lemil-Opitz syndrome, the phenotypic effects on the developing fetus are not solely attributable to the lack of cholesterol but the accumulation of 7-dehydrocholesterol and its 27-hydroxy metabolite. This view is now supported by a new mouse model, the double knockout Insig1 & 2 (insulin-induced genes 1 & 2) in which lack of the protein product results in a greater production of lanosterol compared to cholesterol during fetal life with severe dysmorphic consequences. Further support can be derived from in vitro studies of the Sonic hedgehog signaling pathway, essential for normal morphogenesis in the central nervous system and perhaps other organs, which may require the local presence of oxysterols for full expression. Future studies that can delineate the specific role of a sterol intermediate or its metabolite require a paradigm shift away from the generic use of oxysterols as a class of compounds to a focus on specific sterols that can be expected in tissues and techniques for mimicking the local environment. Another class of oxysterols are those arising by photoxidation, now considered to be an expected event generated by the photons of visible blue light and therefore pari passu with normal vision. The sequence of events from peroxides of cholesterol to hydroxy and keto derivatives is the signature of singlet oxygen as opposed to free radicals and other mechanisms for generating reactive oxygen species. Perhaps surprisingly, the retina expresses CYP 27A1 and CYP 46A1, enzymes with broad substrate specificity for ring-modified sterols, implying that, in addition to a rich blood supply for disposing of potentially toxic oxysterols, they can be detoxified locally. Recognition that the retina has nuclear receptors similar to those found in other tissues raises the possibility that the sterols that are generated may function in their traditional role as ligands for modulating gene expression but other, nonligand, activities can be expected since other proteins such as the oxysterol-binding proteins exist and are considered to have biologic activities. To critically evaluate these potentially new biologic roles for oxysterols a need exists for the synthesis and utilization of the expected naturally occurring metabolites rather than available surrogates that may not be truly representative of their tissue effects and to utilize analytical techniques that can identify their existence at the expected concentrations in tissues.     

Biotechnology in the 21st century

Although the future is unpredictable, it is highly likely that biotechnology will play a much more visible and significant role in the 21st century than it did in the 20th century. The number and kinds of drugs provided by biotechnology will expand markedly and biotechnology will stand at the center of the oncoming revolution in bioinformatics.